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Biomedical subjects

Richard Sutton

Publications and source records attributed to Richard Sutton.

At least 19 recordsLinked to original sources
PubMed2004

Life-years gained from defibrillator implantation: markedly nonlinear increase during 3 years of follow-up and its implications.

BACKGROUND: Although treatment benefit in randomized controlled trials of defibrillators is often summarized by the numbers of lives saved (absolute risk difference), this may not be a good representation of what matters most to patients, namely, the amount of life they should expect to gain from implantation. The estimate of gain in life-years may depend on duration of follow-up. In this study, we examine this dependency. METHODS AND RESULTS: We estimated, from published data of 8 landmark defibrillator trials, the cumulative benefit in life-years gained at time points from 3 months to 3 years. Because the trial populations, clinical status, and prognosis varied widely between studies, we expressed for each study the benefit at each time point as the proportion of benefit at 3 years. The average dependency of the benefit on duration of follow-up was then calculated. We found that the number of life-years gained from 1 device implantation increases with length of follow-up considered. Importantly, this increase is markedly nonlinear. Within the 3-year span addressable, the benefit rises with the square of time (gain infinity t(1.94), R2=0.998, P<0.001). CONCLUSIONS: Measurable benefit from a defibrillator to patients' life spans (life-years gained) is dramatically dependent on the time window over which the benefit is assessed. Because the effort of implantation is front loaded, yet benefit grows with time, the choice of an early time point artificially reduces apparent benefit and artificially increases the apparent number needed to treat to prevent an event. These are useful considerations for the formulation of treatment policy (and even for planning of the follow-up phase of clinical trials).

Clinical Trials as Topic↗
PubMed2004

Syncope.

Syncope is a syndrome consisting of a relatively short period of temporary and self-limited loss of consciousness caused by transient diminution of blood flow to the brain (most often the result of systemic hypotension). Syncope comprises part of a subset of clinical conditions in which loss of consciousness is transient. Other conditions in this group, which are not syncope and should be clearly distinguished from syncope, include, for example, seizure disorders, posttraumatic loss of consciousness, and cataplexy. Recent surveys indicate that syncope accounts for approximately 1% of emergency department visits in Europe, although older reports from the United States placed this number closer to 3%. The reported prevalence of syncope in the population varies: 15% of children before the age of 18 years; 25% of a military population aged 17 to 26 years; 16% and 19%, respectively, in men and women aged 40 to 59 years; and up to 23% in a nursing home population older than 70 years. The highest frequency of syncope occurs in patients with cardiovascular comorbidity and older patients in institutional care settings. The causes of syncope are numerous and, not infrequently, multiple factors may contribute. The diagnostic evaluation is benefited by availability of a detailed medical history and reports of eyewitnesses. In this context, the physician must consider the classification of the causes of syncope, and address the most likely causes first. The principal groups of causes may be summarized as: (1) neurally mediated reflex syncope (eg, vasovagal faint, carotid sinus syndrome); (2) orthostatic (postural) syncope; (3) cardiac arrhythmias; (4) structural cardiac and pulmonary causes; and (5) cerebrovascular disorders (rare). In addition, conditions that may mimic syncope but are not true syncope (eg, psychogenic pseudosyncope) must be considered. Only after a definitive cause is established can appropriate treatment be initiated. In this regard, the syncope evaluation is facilitated by maintaining an organized diagnostic approach. The practitioner should avoid wasteful use of short-term ambulatory electrocardiographic recordings (eg, Holter monitors) and rarely positive neurologic tests (eg, electroencephelography, head magnetic resonance imaging/computed tomography) in the absence of head trauma or evident neurologic signs. In many medical centers the evaluation of patients with syncope is haphazard, and may be substantially enhanced by establishment of a multidisciplinary syncope evaluation unit or team.

Diagnosis, Differential↗
PubMed2004

A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE).

AIMS: Recently, some studies revealed the efficacy of pacemaker implantation in decreasing recurrences in patients with vasovagal syncope. As these studies were not blinded or placebo-controlled, the benefits observed might have been due to a bias in the assessment of outcomes or to a placebo effect of the pacemaker. We performed a randomized, double-blind, placebo-controlled study in order to ascertain if pacing therapy reduces the risk of syncope relapse. METHODS AND RESULTS: Twenty-nine patients (53 +/- 16 years; 19 women) with severe recurrent tilt-induced vasovagal syncope (median 12 syncopes in the lifetime) and 1 syncopal relapse after head-up tilt testing underwent implantation of a pacemaker, and were randomized to pacemaker ON or to pacemaker OFF. During a median of 715 days of follow-up, 8 (50%) patients randomized to pacemaker ON had recurrence of syncope compared to 5 (38%) of patients randomized to pacemaker OFF (p = n.s.); the median time to first syncope was longer in the pacemaker ON than in pacemaker OFF group, although not significantly so (97 [38-144] vs 20 [4-302] days; p = 0.38). There was also no significant difference in the subgroups of patients who had had a mixed response and in those who had had an asystolic response during head-up tilt testing. CONCLUSION: Our data were unable to show a superiority of active pacing versus inactive pacing in preventing syncopal recurrence in patients with severe recurrent tilt-induced vasovagal syncope.

Cardiac Pacing, Artificial↗
PubMed2003

Age and hemodynamic responses to tilt testing in those with syncope of unknown origin.

OBJECTIVES: We sought to determine whether there are age-related differences in vasovagal syncope. BACKGROUND: In those with suspected vasovagal (neurocardiogenic) syncope, tilt testing demonstrates different hemodynamic responses. These responses may be age related, reflecting differing underlying pathophysiology. METHODS: Using a two-stage tilt protocol with glyceryl trinitrate (GTN) provocation, 505 consecutive syncopal patients were studied. Their baseline characteristics and hemodynamic responses during both early and tilt-induced collapse were analyzed. Hemodynamic responses were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed, cardioinhibition, severe cardioinhibition/asystole, pure vasodepression, chronotropic incompetence, and excessive heart rate rise. Multivariate regression analyses were performed to determine the associations of the baseline clinical characteristics (including age) and the tilt-induced hemodynamic responses. RESULTS: Thirty-three patients were unable to tolerate tilt testing. Age was independently associated with distinct responses during tilt. Chronotropic incompetence was predicted by increasing age (odds ratio [OR] 1.04, p < 0.0002). Younger age predicted an excessive heart rate rise (OR 0.97, p < 0.0005). Pure vasodepression was more common in the older group (>65 years; OR 29.5, p < 0.0001), whereas severe cardioinhibition was much less common in the older age group (OR 0.18, p < 0.0001). CONCLUSIONS: There appear to be distinct pathophysiologies underlying vasovagal syncope in different age groups. Young people appear to have excessive cardiac and autonomic responses to stress, whereas older patients appear to have a more generalized cardiovascular decline, with attenuated cardiac and autonomic responses to stress.

Adult↗
PubMed2003

Cardiac pacemaker lead extraction using conventional techniques:a single centre experience.

BACKGROUND: New methods of lead extraction using laser sheath devices are under evaluation but these techniques are not available in the majority of centres and have cost implications. Furthermore, in the absence of comparative randomised trials, registry experience with new devices must be judged against contemporary data using conventional methods. We report a single centre series of pacemaker lead extraction using conventional methods. METHODS STUDY POPULATION: Attempted extraction of 165 leads during 95 procedures in 80 patients. Leads had been in place (dwell time) for a mean of 76 months (range 0.2-248.4 months). Indications for lead extraction: infection (41.1%), skin erosion (9.5%), advisory leads (12.6%), faulty leads (12.6%), other (24.2%). Extraction techniques: traction and/or locking stylets and dilator sheaths (89.7%), Byrd workstation (6.1%) and open thoracotomy (4.8%). RESULTS: Complete removal was achieved for 143 leads (86.7%), partial removal in 12 leads (7.3%) and 10 (6.1%) could not be removed. A shorter lead dwell time was associated with extraction success in both univariate (p=0.0004) and multivariate analyses (p<0.0001). There was a trend for a higher rate of success in atrial rather than ventricular leads (93.2% v 80.9%, p=0.052). Active fixation, patient gender, age and indication for lead extraction had no bearing on outcome. COMPLICATIONS: There were no deaths. Major complications occurred in 3 patients (3.2%): pericardial tamponade (1), pulmonary embolus (1) and stroke (1). Significant bleeding (requiring blood transfusion) occurred in 11 procedures (12%). CONCLUSIONS: Cardiac lead extraction using conventional methods has a high success rate of 86.7%. Success was significantly related to a shorter lead dwell time. Further prospective randomised trials are needed to compare traditional techniques with laser extraction both in terms of clinical outcome and cost-effectiveness.

Adolescent↗
PubMed2002

Engraftment of sorted/expanded human central nervous system stem cells from fetal brain.

Direct isolation of human central nervous system stem cells (CNS-SC) based on cell surface markers yields a highly purified stem cell population that can extensively expand in vitro and exhibit multilineage differentiation potential both in vitro and in vivo. The CNS-SC were isolated from fetal brain tissue using the cell surface markers CD133(+), CD34(-), CD45(-), and CD24(-/lo) (CD133(+) cells). Fluorescence-activated cell sorted (FACS) CD133(+) cells continue to expand exponentially as neurospheres while retaining multipotential differentiation capacity for >10 passages. CD133(-), CD34(-), and CD45(-) sorted cells (approximately 95% of total fetal brain tissue) fail to initiate neurospheres. Neurosphere cells transplanted into neonatal immunodeficient NOD-SCID mice proliferated, migrated, and differentiated in a site-specific manner. However, it has been difficult to evaluate human cell engraftment, because many of the available monoclonal antibodies against neural cells (beta-tubulin III and glial fibrillary acidic protein) are not species specific. To trace the progeny of human cells after transplantation, CD133(+)-derived neurosphere cells were transduced with lentiviral vectors containing enhanced green fluorescent protein (eGFP) expressed downstream of the phosphoglycerate kinase promoter. After transduction, GFP(+) cells were enriched by FACS, expanded, and transplanted into the lateral ventricular space of neonatal immunodeficient NOD-SCID brain. The progeny of transplanted cells were detected by either GFP fluorescence or antibody against GFP. GFP(+) cells were present in the subventricular zone-rostral migrating stream, olfactory bulb, and hippocampus as well as nonneurogenic sites, such as cerebellum, cerebral cortex, and striatum. Antibody against GFP revealed that some of the cells displayed differentiating dendrites and processes with neurons or glia cells. Thus, marking human CNS-SC with reporter genes introduced by lentiviral vectors is a useful tool with which to characterize migration and differentiation of human cells in this mouse transplantation model.

Animals↗
PubMed2002

The effect of the localization of Q wave myocardial infarction on ventricular electromechanics.

BACKGROUND: The exact location of a Q wave myocardial infarction has an important effect on overall left ventricular function. OBJECTIVES: To assess the effect of localization of Q wave infarction on left ventricular minor and long axis function, with particular reference to electromechanical disturbances. METHODS: We studied 72 patients with Q wave myocardial infarction; 35 anterior, age 61+/-15 years and 37 inferior, age 62+/-12 years. ECG intervals were automatically measured by Hewlett-Packard Pagewriter and LV dimension and filling velocities studied by transthoracic echocardiography and simultaneous phonocardiogram. Findings were compared with 21 controls of similar age. RESULTS: Heart rate and all ECG intervals were similar in the two patient groups and controls. QRS axis was more to the left in patients with inferior MI. Normal septal q wave was absent in lead V5 and V6 in 33/35 (94%) patients with anterior MI and in only 3/37 (8%) with inferior MI, p<0.001. LV minor axis dimensions were enlarged vs. normal (p<0.001) in the two patient groups and to a greater extent in anterior MI compared with inferior MI, p<0.05. Isovolumic relaxation time was prolonged only in-patients with an inferior MI, p<0.01. Long axis amplitude was globally reduced (p<0.001) in the two patient groups as were shortening and lengthening velocities (p<0.001). The onset of septal long axis shortening with respect to the q wave was delayed by 30 and 40 ms in inferior MI and anterior MI and that of lengthening with respect to A2 by 20 and 30 ms, respectively, compared to normal (p<0.001 for both). Post ejection shortening was localized to the septal long axis in 32/35 patients with anterior MI but was generalized involving all three LV long axes in inferior MI, p<0.001. Transmitral Doppler flow velocities and the frequency of mild mitral regurgitation were similar in the two groups. CONCLUSION: These results confirm a close association between anterior Q wave infarction, septal incoordination and absent septal q waves. The global incoordinate long axis behaviour in inferior Q wave MI may be due to significant papillary muscle dysfunction, and results in significant shape change in early diastole. This disturbance in electromechanical behaviour might play an important role in the differing outcomes between the two different sites of myocardial infarction.

Aged↗
PubMed2002

Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer.

BACKGROUND: Lymphoscintigraphy and sentinel node biopsy are currently being assessed as an alternative to axillary dissection for staging in early breast cancer. However, little is known about the optimum timing of surgery following injection of the radio-isotope into the breast. The aim of the present study was to establish whether lymphoscintigraphy on the morning of surgery allowed efficacious and accurate sentinel node identification and biopsy. METHODS: We reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early breast cancer using peritumoural injections of technetium99m antimony sulphide colloid and subsequent sentinel node biopsy using a hand-held gamma probe and blue dye. The time interval between radioisotope injection and successful intraoperative identification of the sentinel node was assessed and whether this was associated with certain clinical and histological variables. RESULTS: The sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median time duration of 40 min post injection. The median time duration between isotope injection and surgery was 5 h. Of the 160 cases where the sentinel node was visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy failed to localize the sentinel node (P < 0.0001). There was no association found between the injection of the radioisotope greater or less than 5 h before surgery and the successful intraoperative identification of the sentinel node. Failure to identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a low intraoperative identification rate. There was no correlation found between intraoperative identification of the sentinel node according to the duration of isotope injection in relation to surgery and the various clinical and histological factors assessed. CONCLUSIONS: In our experience, the chance of identifying the sentinel node at the time of surgery does not increase with longer isotope injection duration using technetium99m antimony sulphide colloid. As soon as a sentinel node is identified at lymphoscintigraphy, one can proceed to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node localization. Given that the median time for successful lymphoscintigraphic mapping was only 40 min, lymphoscintigraphy can easily be completed during the morning to allow surgery to take place the same day.

Adult↗
PubMed2002

How to test mode switching in pacemakers implanted in patients: the MOST study.

Optimal management of atrial arrhythmias with dual chamber pacemakers requires proper performance of automatic mode switching (AMS). The aim of this study was to develop a reliable technique to test the AMS function by using an external electronic device capable of mimicking the occurrence of supraventricular arrhythmias (Supraventricular Arrhythmia Simulator [SAS]). The SAS delivers low voltage pulse trains (200 mV, 20 ms) through two skin electrodes. Each pulse train lasts 15 seconds and starts synchronously with a pacing pulse of the implanted pacemaker to avoid interference from the operator. The pulse train rate is set at 350, 250, and 160 beats/min to simulate AF, atrial flutter, and atrial tachycardia (AT), respectively. Thirty-five patients implanted with Vitatron pacemakers, whose AMS system has been previously validated, were enrolled. Atrial and ventricular sensing were programmed in unipolar mode at 0.5 mV and in bipolar mode at > 2 mV, respectively. All pulses from the SAS were detected by the atrial channel at an amplitude ranging from 1 to 3 mV. The test proved to be safe and reliable at rest and during exercise. AMS occurred immediately at onset or at offset of atrial arrhythmias, and no adverse interference on pacemaker function was seen from the SAS. In conclusion, the described technique and the SAS are safe and reliable for patient and pacemaker function and can be proposed as a useful method to verify proper performance of AMS function irrespective of the type of implanted devices.

Aged↗
PubMed2002

The revised NASPE/BPEG generic code for antibradycardia, adaptive-rate, and multisite pacing. North American Society of Pacing and Electrophysiology/British Pacing and Electrophysiology Group.

In light of evolving pacemaker technology and increasing interest in multisite pacing, the Committee on the Development of Position Statements (CDPS) of the North American Society of Pacing and Electrophysiology (NASPE) created an ad hoc Pacemaker Mode Code Task Force in April 2001 under the chairmanship of David L. Hayes, MD, for the purpose of bringing the NASPE/British Pacing and Electrophysiology Group (BPEG) Generic Pacemaker Code (NBG Code) up to date. The task force, whose members are the authors of this article, designed a revised NBG Code in which three major issues were taken into account. First, it was recognized that all modern pacemakerpulse generators are capable of extensive bidirectional communication with an external programming device, making them "communicating" pulse generators as defined by the current (1987) NBG Code. Second, it was decided that a means of providing basic information regarding the location of multisite pacing would be a useful ingredient of the NBG Code. Third, in view of the extensive antibradycardia pacing capabilities common in modern implantable cardioverter defibrillators and the availability of the NASPE/BPEG Defibrillator Code (NBD Code), it was considered unnecessary for the NBG Code to address the presence or absence of antitachycardia features. The resulting updated version of the NBG Code as described herein was endorsed by the BPEG on September 20, 2001 and adopted by the NASPE Board of Trustees on October 18, 2001. The structure of the revised NBG Code differs from that of the previous version in two respects alone: Position IV specifies only the presence or absence of rate modulation, and Position V specifies only the location or absence of multisite pacing (i.e., biatrial or biventricular pacing with at least two stimulation sites in each case) more than one stimulation site in any single cardiac chamber, or any combination of these. The revised NBG Code is deliberately configured to avoid confusion with earlier mode codes, and it is the authors' hope that it will serve as an enhanced resource for communication among those engaged in every phase of the multidisciplinary practice of cardiac rhythm management.

Bradycardia↗
PubMed2002

Sentinel node biopsy and lymphoscintigraphy with a technetium 99m labeled blue dye in a rabbit model.

BACKGROUND: Lymphatic mapping for sentinel node biopsy in breast cancer and melanoma usually involves initial peritumoral injection of a radioisotope, gamma camera detection of the sentinel lymph node several hours prior to the operation, and separate perioperative injection of a blue dye. We have developed a combined approach using technetium 99m labeled blue dye (Evans Blue) for use in lymphoscintigraphy that may be injected as a single dose just prior to the operation. METHODS: In an anesthetized rabbit model we dissected a hind limb to display the popliteal node and afferent lymphatic. Technetium 99m Evans Blue ((99m)Tc-EB) (22 MBq; 0.5 mL) was injected subdermally in the dorsum of the paw. Simultaneous digital and gamma camera images were obtained at 14 time intervals to 30 minutes post injection. For each of these time intervals the percentage of radioactivity and percentage blueness of the popliteal node were determined. Urine and afferent lymphatic fluid were analyzed by chromatography. The popliteal node was excised post mortem, placed into solvent solutions and analyzed for blueness and radioactivity. RESULTS: Time-activity curves for radioactivity and time-blueness curves for Evans Blue uptake showed strong correlation (r = 0.958). Lymph analysis suggested (99m)Tc-EB is mainly bound to endogenous proteins. Urine was radioactive but not colored, (99m)Tc-EB being metabolized and excreted in the urine as 1,7-diamino-8-naphthol-2,4-disulfonic acid. Prolonged exposure of node to solvents did not dissociate any blue coloration or radioactivity. CONCLUSIONS: (99m)Tc-EB and Evans Blue are simultaneously retained and concentrated in the sentinel lymph node. This process is rapid and reproducible. (99m)Tc-EB migrates at the same rate as Evans Blue in lymph, where it is transported as bound to endogenous proteins. These dye molecules are metabolized by reductive cleavage in the liver and then excreted renally as colorless, radioactive metabolites. This novel agent has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for a range of solid malignancies including breast cancer and melanoma.

Animals↗
PubMed2002

How and when to pace in vasovagal syncope.

This article discusses the indications for pacing in vasovagal syncope. It also reviews the literature on pacing results; notably, there are two small randomized controlled trials of pacing versus no therapy (or continued nondevice therapy) that show a clear benefit for pacing. The mode of benefit is, as yet, unclear. Pacing has to be dual chamber with some form of rate hysteresis. Ways of improving pacemaker therapy delivery in vasovagal syncope are anticipated.

Blood Pressure↗